RESUMEN
A symptom-free woman gave birth to a girl with a low carnitine level on newborn screening. The baby was unaffected, but the mother had biochemical abnormalities and mutations characteristic of the cblC defect of vitamin B(12) metabolism (late-onset form). This patient with cblC was detected through her infant's newborn screening.
Asunto(s)
Carnitina/metabolismo , Homocistinuria/diagnóstico , Tamizaje Neonatal , Trastornos Puerperales/diagnóstico , Adulto , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Femenino , Homocistinuria/genética , Homocistinuria/metabolismo , Humanos , Recién Nacido , Oxidorreductasas , Trastornos Puerperales/genética , Trastornos Puerperales/metabolismoRESUMEN
OBJECTIVES: To describe 3 patients with the cblD disorder, a rare inborn error of cobalamin metabolism caused by mutations in the MMADHC gene that can result in isolated homocystinuria, isolated methylmalonic aciduria, or combined homocystinuria and methylmalonic aciduria. STUDY DESIGN: Patient clinical records were reviewed. Biochemical and somatic cell genetic studies were performed on cultured fibroblasts. Sequence analysis of the MMADHC gene was performed on patient DNA. RESULTS: Patient 1 presented with isolated methylmalonic aciduria, patient 3 with isolated homocystinuria, and patient 2 with combined methylmalonic aciduria and homocystinuria. Studies of cultured fibroblasts confirmed decreased synthesis of adenosylcobalamin in patient 1, decreased synthesis of methylcobalamin in patient 3, and decreased synthesis of both cobalamin derivatives in patient 2. The diagnosis of cblD was established in each patient by complementation analysis. Mutations in the MMADHC gene were identified in all patients. CONCLUSIONS: The results emphasize the heterogeneous clinical, cellular and molecular phenotype of the cblD disorder. The results of molecular analysis of the MMADHC gene are consistent with the hypothesis that mutations affecting the N terminus of the MMADHC protein are associated with methylmalonic aciduria, and mutations affecting the C terminus are associated with homocystinuria.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/genética , Cobamidas/deficiencia , Deficiencia de Vitamina B 12/diagnóstico , Deficiencia de Vitamina B 12/genética , Errores Innatos del Metabolismo de los Aminoácidos/fisiopatología , Células Cultivadas , Salud de la Familia , Femenino , Fibroblastos/metabolismo , Homocistinuria/genética , Homocistinuria/fisiopatología , Humanos , Recién Nacido , Péptidos y Proteínas de Señalización Intracelular , Masculino , Proteínas de Transporte de Membrana/genética , Ácido Metilmalónico/metabolismo , Proteínas de Transporte de Membrana Mitocondrial , Proteínas Mitocondriales/genética , Fenotipo , Deficiencia de Vitamina B 12/fisiopatologíaRESUMEN
A neonate with elevated propionylcarnitine on the newborn screen was found to have methylmalonic acidemia due to vitamin B(12) deficiency. The mother was also vitamin B(12)-deficient. This case illustrates the utility of expanded newborn screening for detection of vitamin B(12) deficiency, allowing prompt treatment and prevention of potential sequelae.